Mahomes made his major league debut with the Twins in 1992. He made the team out of spring training, and started the sixth game of the season on April 12 against the Texas Rangers, pitching six innings and getting a no decision.[2] He notched his first major league win in his next start on April 21 against the Seattle Mariners.[3] Mahomes played with the Twins into the 1996 season, appearing in a total of 114 games (51 starts) during five seasons while compiling an 18–28 record with 5.82 ERA, with 217 strikeouts in ​3662⁄3 innings. The Twins traded Mahomes to the Red Sox on August 26, 1996, in exchange for a player to be named later (which turned out to be pitcher Brian Looney).[4]

Mahomes pitched a total of 21 games (all in relief) during the 1996 and 1997 seasons with Boston, registering a 6.85 ERA with 3–0 record and 11 strikeouts in ​221⁄3 innings. He was released by the Red Sox on June 27, 1997.[4]

Mahomes was signed by the Mets in December 1998.[4] He went 8-0 in the 1999 season during 39 relief appearances, and helped the Mets reach the playoffs. Mahomes made four relief appearances during the postseason, recording a 2.25 ERA in eight innings pitched while striking out four, as the Mets lost to the Atlanta Braves in the NLCS. In 2000, Mahomes was 5–3 in 53 appearances (five starts), and while the Mets reached the 2000 World Series, Mahomes was left off the Mets' playoff roster. In his two seasons with the Mets, Mahomes appeared in 92 regular season games (five starts) with a 4.74 ERA, 13–3 record, and 127 strikeouts in ​1572⁄3 innings. He became a free agent in December 2000.[4]

Mahomes signed with the Rangers in January 2001. During the 2001 season, he appeared in 56 games (four starts) with a 5.70 ERA and 7–6 record, while striking out 61 in ​1071⁄3 innings. Mahomes again became a free agent in November 2001.[4]

In January 2002, Mahomes signed with the Cubs. He made 16 appearances (two starts) during the 2002 season, with a 3.86 ERA and 1–1 record, striking out 23 in ​322⁄3 innings. Mahomes became a free agent in October 2002.[4]

Mahomes was signed by Pittsburgh in January 2003. He made nine appearances (one start) with the Pirates during the 2003 season, recording an 0–1 record with 4.84 ERA and 13 strikeouts in ​221⁄3 innings. This would prove to be his final season playing in MLB. Mahomes again became a free agent in September 2003.[4]

Overall, Mahomes pitched 11 seasons in MLB, making a total of 308 regular season appearances (63 starts) with a 42–39 record, 5.47 ERA, and 452 strikeouts in 709 innings pitched. He had 43 at bats during his career, with 11 hits (.256 batting average) and four RBIs.

Mahomes signed with the Southern Maryland Blue Crabs of the Atlantic League in 2008, but only appeared in two games for them before returning to Sioux Falls. He split the 2009 season between Sioux Falls and Grand Prairie.